Metabolomics Study on the Antitumor Effect of Osthole on HepG2 Cells Using UPLC-Q-TOF-MS/MS

Hepatocellular carcinoma (HCC) stands as a globally common malignancy with persistently elevated incidence and mortality rates. It is known for being able to resist conventional chemotherapy. There is currently growing interest in natural products for the treatment of HCC, owing to their significant antitumor activity. Osthole, a naturally occurring O-methylated coumarin in Cnidium monnieri (L.) Cusson, showed potent antitumor effects on various types of cancer. It plays a therapeutic role in HCC by inducing apoptosis and inhibiting proliferation. Nevertheless, the anti-HCC effect of osthole at the molecular level needs to be investigated. In this study, an ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS)–based cell metabolomics approach was established to investigate the antitumor effect of osthole on HepG2 cells. The effect of osthole on the viability of HepG2 cells was found to be concentration and time-dependent. Moreover, 43 differential metabolites were identified, involving the metabolic pathways of sphingolipid, glycerophospholipid, and tryptophan. It is suggested that osthole may have an anti-HCC effect by affecting the function of normal cells, altering important cellular properties, reducing cellular activity, and inducing cellular apoptosis.